V. Treatment of Current (Active) Disease Therapy
Last Updated April 2026
Treatment of persons living with HIV with active TB disease should be carried out in consultation with a physician who has experience in the use of rifamycin drugs and antiretroviral agents. Recommendations on the treatment of TB in combination with antiretroviral therapy continue to evolve, and it is important to check for updated guidelines: https://clinicalinfo.hiv.gov/en/guidelines and https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tuberculosishiv-coinfection?view=full
Antiretroviral therapy (ART)⌃- Improves outcomes for persons living with HIV and decreases HIV-related mortality as well as risk of relapse. Persons living with HIV in the United States with active TB disease commonly have advanced HIV/AIDS with low CD4 counts and high plasma HIV RNA levels; all patients with TB who have HIV co-infection should receive treatment for HIV with ART.
- Multiple studies have demonstrated the benefits of ART initiation among persons living with HIV during TB treatment, including a reduction in mortality.
- However, the use of ART among persons living with HIV with active TB disease is complicated by overlapping toxicity profiles of some antituberculosis and antiretroviral drugs; complex drug-drug interactions; and the occurrence of “paradoxical” reactions or immune reconstitution inflammatory syndrome (IRIS).
- CD4 T lymphocyte (CD4) cell counts <50 cells/mm3: HHS guidelines recommend initiating ART as soon as possible, but within 2 weeks of starting TB treatment.
- CD4 counts ≥50 cells/mm3: Initiate ART within 2 to 8 weeks of starting TB treatment.
- During pregnancy, regardless of CD4 count: Initiate ART as early as feasible for treatment of the person with HIV and prevention of HIV transmission to the infant.
- With TB meningitis: Initiate ART after TB meningitis is under control and after at least 2 weeks of anti-TB treatment to reduce the risk of life-threatening inflammation in a closed space (i.e., brain) as a result of immune reconstitution. Generally, initiation of ART in this setting is recommended 4 to 8 weeks after initiation of therapy for TB meningitis.
As noted above, there are certain situations where ART therapy should be delayed when treating persons with active TB disease who have HIV co-infection. A study of people living with HIV with TB meningitis found that early ART was associated with an increase in severe adverse events and no mortality benefit. Thus, timing of ART initiation in persons with active TB disease who have HIV co-infection should take into account both the degree of immune suppression and site of disease (see Table 13 and recommendations above).
Table 13. Antiretroviral Therapy (ART) and Treatment of Persons Living with HIV and Active TB
| HHS Panel Recommendations on treatment of Tuberculosis Disease with HIV co-infection: Timing of Antiretroviral Therapy (ART) Initiation relative to TB treatment | |
|---|---|
| CD4 count and/or clinical status at time of TB diagnosis | ART Initiation |
| < 50 cells/mm³ | within 2 weeks of starting TB therapy. |
| > 50 cells/mm³ | by 8 to 12 weeks of starting TB therapy |
| Pregnant, any CD4 count | As early as feasible |
Above based on guidelines developed by the Department of Health and Human Services (DHHS) Panel on Guidelines for Use of Antiretroviral Agents for Adults and Adolescents and Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal Transmission in the United States, last reviewed and updated April 15, 2019
(https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium?view=full).
Table 14. Antiretroviral Therapy (ART) and Treatment of Persons Living with HIV and Active TB
Principle: Despite Drug Interactions, a Rifamycin (Rifampin or Rifabutin) Should Be Included in TB Regimens for Patients Receiving ART, with Dosage Adjustment if Necessary
Integrase-based ART regimens. Dolutegravir is the preferred integrase for TB/HIV co-infection treatment.
1a. Patients receiving rifampin-based TB treatment.
| Preferred | DTG (Tivicay) BID + TDF/FTC (Truvada) |
|---|---|
| Alternative |
|
| Frequency | Daily for both preferred and alternative |
| Note | Triumeq is a combination of DTG/ABC/3tc |
1b. Patients receiving rifabutin-based TB treatment
| Preferred | DTG (Tivicay) + TDF/FTC (Truvada) |
|---|---|
| Alternative |
|
| Frequency | Daily for both preferred and alternative |
| Note | The FDA does not recommend using TAF with rifampin or rifabutin |
Abbreviations:
- NRTIs: nucleoside/-tide reverse transcriptase inhibitors
- NNRTIs: non-nucleoside reverse transcriptase inhibitors
- PIs: protease inhibitors
- /r: boosted with ritonavir
- TDF: Tenofovir disoproxil fumarate
- TAF: Tenofovir alafenamide
- FTC: Emtricitabine
- 3TC: Lamivudine
- ABC: Abacavir
- ATV/r: Atazanavir/ritonavir
- DRV/r: Darunavir/ritonavir
- DTG: Dolutegravir
Source:
- Above based on guidelines developed by the Department of Health and Human Services (DHHS) Panel on Guidelines for Use of Antiretroviral Agents for Adults and Adolescents and Use of Antiretroviral Drugs in Pregnant Women living with HIV and Interventions to Reduce
- Perinatal Transmission in the United States, last reviewed and updated October 29, 2024 (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium?view=full).
PI-based ART regimens (cannot be used with rifampin, must use with dose-adjusted rifabutin)
2a
| Preferred | ATV/r + TDF/FTC (Truvada) |
|---|---|
| Alternative |
|
| Frequency | Daily for both preferred and alternative |
2b
| Preferred | DRV/r + TDF/FTC (Truvada) |
|---|---|
| Alternative |
|
| Frequency | Daily for both preferred and alternative |
Additional Notes:
- PI’s have high barrier to resistance. However, given rifabutin is given at half-dose when used with PI’s adherence to ART should be closely monitored. Poor adherence to PI’s while on rifabutin increases risk for rifampin resistance.
- The FDA does not recommend using TAF with rifampin or rifabutin.
- Cobicistat cannot be used with rifabutin.
Abbreviations:
- NRTIs: nucleoside/-tide reverse transcriptase inhibitors
- NNRTIs: non-nucleoside reverse transcriptase inhibitors
- PIs: protease inhibitors
- /r: boosted with ritonavir
- TDF: Tenofovir disoproxil fumarate
- TAF: Tenofovir alafenamide
- FTC: Emtricitabine
- 3TC: Lamivudine
- ABC: Abacavir
- ATV/r: Atazanavir/ritonavir
- DRV/r: Darunavir/ritonavir
- DTG: Dolutegravir
Source:
- Above based on guidelines developed by the Department of Health and Human Services (DHHS) Panel on Guidelines for Use of Antiretroviral Agents for Adults and Adolescents and Use of Antiretroviral Drugs in Pregnant Women living with HIV and Interventions to Reduce
- Perinatal Transmission in the United States, last reviewed and updated October 29, 2024 (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium?view=full).
Choice for Pregnant Women living with HIV and with Active TB
2a
| Notes |
|
|---|
Source:
- Above based on guidelines developed by the Department of Health and Human Services (DHHS) Panel on Guidelines for Use of Antiretroviral Agents for Adults and Adolescents and Use of Antiretroviral Drugs in Pregnant Women living with HIV and Interventions to Reduce
- Perinatal Transmission in the United States, last reviewed and updated October 29, 2024 (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium?view=full).
Persons who are already on ART at the time of TB diagnosis, generally should be continued on the ART treatment (though ART regimen may need to be adjusted).
Choice of ART⌃
- Because of the potential for significant drug interactions and overlapping toxicities, the choice of ART among persons living with HIV who have active TB disease should be made only after direct communication between HIV and tuberculosis care providers.
- Any change in either the TB medications or the ART regimen should be immediately shared between the two providers.
There are clinically important drug-drug interactions between the rifamycins (e.g., rifampin, rifabutin, rifapentene) and some of the antiretroviral drugs, especially integrase and protease inhibitors.⌃
- The rifamycins are inducers of the cytochrome P450-3A (CYP3A) system in the liver and thereby decrease serum concentrations of drugs metabolized by this system including integrase and protease inhibitors.
- Rifampin is a potent inducer of the CYP3A, while rifabutin is a less potent inducer. Rifampin cannot be given with most protease inhibitors because it results in low serum levels of these drugs.
- Rifabutin has less of an effect and therefore can be used with certain protease inhibitors as described below.
- Rifampin and rifabutin can be given with certain integrase inhibitors (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/coinfections-tuberculosis-hiv).
The protease inhibitors also affect rifamycin metabolism and because the rifamycin metabolism is retarded by these drugs, the dose of rifabutin needs to be reduced in order to avoid rifabutin related toxicity.
Despite these drug-drug interactions, a rifamycin (rifampin or rifabutin) should ALWAYS be included in the treatment regimen for drug-susceptible TB among persons living with HIV.
Rifampin can be given with the following antiretrovirals:⌃
- MOST Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) (e.g., zidovudine, lamivudine, emtricitabine, tenofovir disoproxil fumarate (TDF), abacavir). Tenofovir alafenamide (TAF) is not currently recommended for use in combination with rifamycins.
- SELECTED Non-nucleoside reverse transcriptase inhibitors (NNRTIs): efavirenz only (all others are contraindicated for coadministration with rifampin).
- Selected Integrase inhibitors: raltegravir and dolutegravir. The dose of raltegravir must be increased to 800 mg twice daily (BID) and the dose of dolutegravir must be increased to 50 mg BID for patients on rifampin. Neither raltegravir or dolutegravir require a dosing change when used with rifabutin. Bictegravir (a component of Biktarvy) should NOT be given in combination with any rifamycin drugs (rifampin, rifabutin, rifapentine).
Rifampin should NOT be used with the following:⌃
- Tenofoviral afenamide (TAF)
- Protease inhibitors
- Nevirapine, etravirine, rilpivarine (NNRTIs)
- Bictegravir (including Biktarvy), elvitegravir
A summary of preferred treatment options for patients with tuberculosis disease who are HIV co-infected is shown in Table 15 and Table 16. For additional information refer to updated HHS guidelines, visit https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tuberculosishiv-coinfection?view=full
Table 15. Summary of Recommendations for Treatment of Active TB Disease in Persons with HIV
When to start ART
| What to do |
|
|---|---|
| Key details/caveats |
Early ART ↓ mortality. CNS TB early ART ↑ severe IRIS risk. |
How to prevent IRIS in TB/HIV
| What to do |
|
|---|---|
| Key details/caveats | Contraindicated for patients with rifampin-resistant TB, Kaposi sarcoma, or active hepatitis B. |
TB Regimen: Drug-susceptible TB (DS_TB)
| What to do | Use standard 6-month HRZE → HR regimen (intensive phase 2 months HRZE, continuation phase 4-7 months HR) |
|---|---|
| Key details/caveats | Remains the global standard for HIV-associated TB |
Core ART principles with rifamycins
| What to do | Rifamycins (rifampin, rifabutin, rifapentine) are the most important TB drug in the treatment of DS-TB and every effort should be made to include them in the treatment regimen. However, rifamycins have many drug-drug interactions. |
|---|---|
| Key details/caveats | Rifamycins strongly induce CYP3A, UGT, P-gp, causing major ARV interactions. |
INSTIs with rifamycin
| What to do | Dolutegravir (DTG): Increase does to 50 mg twice daily while on rifampin. Bictegravir (BIC) (INSTI in Biktarvy) is contraindicated with rifampin and other rifamycins. |
|---|---|
| Key details/caveats |
|
NNRTIs with rifampin
| What to do | Efavirenz 600 mg daily is compatible. |
|---|---|
| Key details/caveats | Efavirenz generally maintained at therapeutic levels with rifampin. |
Boosted PIs with rifampin
| What to do | Do NOT use rifampin with ritonavir- or cobicistat-boosted PIs. Use rifabutin instead of rifampin if PI required (can use with ritonavir, cannot use with cobicistat). |
|---|---|
| Key details/caveats |
|
NRTI backbone
| What to do | Use TDF/FTC (Truvada) or 3TC. General recommendations are to avoid TAF (i.e., TAF/FTC [Descovy]) use with rifamycins. However, TAF can be used with rifampin with caution and close monitoring of virologic response per the DHHS/NIH HIV treatment guidelines. |
|---|---|
| Key details/caveats | Rifamycins lower plasma TAF concentration, but intracellular levels are preserved. |
TB-IRIS
| What to do | Continue ART. NSAIDs for mild IRIS. Prednisone for moderate–severe IRIS. |
|---|---|
| Key details/caveats | ART should NOT be stopped except in life-threatening IRIS. |
TB Meningitis
| What to do | Use adjunctive steroids. Delay start of ART. Seek expert advice as CNS TB IRIS may increase morbidity and mortality |
|---|---|
| Key details/caveats | Reduces mortality and CNS IRIS. |
Abbreviations:
- ART – Antiretroviral therapy
- ARV – Antiretroviral
- BIC – Bictegravir
- CNS – Central nervous system
- CYP3A / CYP3A4 – Major drug-metabolizing enzymes
- DS-TB – Drug-susceptible TB
- DTG – Dolutegravir
- EFV – Efavirenz
- FTC – Emtricitabine
- HRZE – TB intensive-phase regimen:
- H = Isoniazid
- R = Rifampin
- Z = Pyrazinamide
- E = Ethambutol
- IRIS – Immune reconstitution inflammatory syndrome
- INSTI – Integrase strand transfer inhibitor
- NNRTI – Non-nucleoside reverse transcriptase inhibitor
- NRTI – Nucleoside/nucleotide reverse transcriptase inhibitor
- PI – Protease inhibitor
- P-gp – P-glycoprotein (drug efflux transporter)
- RFB (or RIFB) – Rifabutin
- RPT – Rifapentine
- TAF – Tenofovir alafenamide
- TDF – Tenofovir disoproxil fumarate
- TB-IRIS – TB-associated immune reconstitution inflammatory syndrome
- UGT (UDP-glucuronosyltransferase): A liver enzyme family that metabolizes many drugs. Rifamycins induce UGT1A1, lowering levels of drugs like dolutegravir and bictegravir.
Source:
- A useful resource is the University of Liverpool HIV Drug Interactions tracker. Available at https://www.hiv-druginteractions.org/?utm_source=chatgpt.com
- Updated guidelines on treatment of active TB in persons with HIV and guidelines for dosage adjustments is available at the following website: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/coinfections-tuberculosis-hiv
Table 16. Guidelines for Treatment of Extrapulmonary Tuberculosis
| Length of therapy | 6 months |
|---|---|
| Corticosteroids | Not recommended |
| Additional management considerations | Pursue microbiologic proof of diagnosis prior to starting Rx |
| Length of therapy | 6 to 9 months |
|---|---|
| Corticosteroids | Not recommended |
| Additional management considerations | Extend to 12 months if hardware is present |
| Length of therapy | 6 to 9 months |
|---|---|
| Corticosteroids | Not recommended for TB rx but may be indicated for cord compression |
| Additional management considerations | Most spine infection can be cured with medical Rx. Surgery indicated for relief of cord compression, progressive disease despite medical therapy, instability of the spine. |
| Length of therapy | 9 to 12 months |
|---|---|
| Corticosteroids | Strongly recommended |
| Steroid dosing | A and C ≥ 25kg: 12 mg/day of dexamethasone x 3 weeks followed by 3-week taper
C < 25kg: 8 mg/day of dexamethasone for 3 weeks followed by 3-week taper |
| Additional management considerations | Most spine infection can be cured with medical Rx. Surgery indicated for relief of cord compression, progressive disease despite medical therapy, instability of the spine. |
| Length of therapy | 9-12 months |
|---|---|
| Corticosteroids | Strongly recommended |
| Additional management considerations | Negative CSF culture or PCR test does NOT exclude this diagnosis
Follow CSF profile for response to therapy |
| Length of therapy | 6 months |
|---|---|
| Corticosteroids | Not recommended |
| Additional management considerations | Empyema may require decortication |
| Length of therapy | 6 months |
|---|---|
| Corticosteroids | NO LONGER routinely RECOMMENDED |
| Additional management considerations | Consider steroids for patients at highest risk of later constriction: large pericardial effusions high levels of inflammatory cells or markers in pericardial fluid those with early signs of constriction |
| Length of therapy | 6 months |
|---|---|
| Corticosteroids | Not recommended |
| Additional management considerations | Obtain cultures from blood, urine and sputum in addition to clinically apparent sites of disease. |
| Length of therapy | 6 months |
|---|---|
| Corticosteroids | Not recommended |
| Additional management considerations |
| Length of therapy | 6 months |
|---|---|
| Corticosteroids | Not recommended |
| Additional management considerations |
2 mg/kg prednisone daily over three weeks, followed by taper Maximum dose 60 mg
OR
Dexamethasone 0.3-0.6 mg/kg daily over three weeks, followed by taper Round to nearest tablet size
(2, 4, 6 mg) Maximum dose 12 mg